Brain cell-specific origin of circulating microRNA biomarkers in experimental temporal lobe epilepsy DOI Creative Commons
Elizabeth Brindley, Mona Heiland, Catherine Mooney

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: Sept. 22, 2023

The diagnosis of epilepsy is complex and challenging would benefit from the availability molecular biomarkers, ideally measurable in a biofluid such as blood. Experimental human are associated with altered brain blood levels various microRNAs (miRNAs). Evidence lacking, however, to whether any circulating pool miRNAs originates brain. To explore link between pathophysiology epilepsy, we first sequenced argonaute 2 (Ago2)-bound plasma samples collected mice subject status epilepticus induced by intraamygdala microinjection kainic acid. This identified time-dependent changes known neuronal microglial-cell origins. had originated brain, generated expressing FLAG-Ago2 neurons or microglia using tamoxifen-inducible Thy1 Cx3cr1 promoters, respectively. FLAG immunoprecipitates these after seizures contained miRNAs, including let-7i-5p miR-19b-3p. Taken together, studies confirm that portion experimental increasing support for mechanistic biomarkers epilepsy.

Language: Английский

mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment DOI
Teresa Ravizza,

Mirte Scheper,

Rossella Di Sapia

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(5), P. 334 - 350

Published: March 26, 2024

Language: Английский

Citations

28
New epilepsy therapies in development DOI
Pavel Klein, Rafal M. Kaminski, Matthias J. Koepp

et al.

Nature Reviews Drug Discovery, Journal Year: 2024, Volume and Issue: 23(9), P. 682 - 708

Published: July 22, 2024

Language: Английский

Citations

28
‘Splice-at-will’ Cas12a crRNA engineering enabled direct quantification of ultrashort RNAs DOI Creative Commons

Xinrui Fei,

Chao Lei, Wei Ren

et al.

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(2)

Published: Jan. 11, 2025

Abstract We present a robust ‘splice-at-will’ CRISPR RNA (crRNA) engineering mechanism that overcomes the limitations of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system in directly detecting ultrashort RNAs. In this strategy, an intact Cas12a crRNA can be split from almost any site spacer region to obtain truncated (tcrRNA) cannot activate even after binding auxiliary DNA activator. While splicing tcrRNAs with moiety RNA, formed combination work together efficiently, enabling engineering. Importantly, exhibits same trans-cleavage activation efficiency as conventional crRNA. Therefore, by rationally designing activator conserved tcrRNA-complementary sequence and arbitrary RNA-of-interest recognition domain, general sensing is established utilizes traditional DNA-activated detect This strategy could faithfully sequences 6–8 nt, which achieved Cas13a systems. Additionally, through flexible design, our method precisely distinguish single-base differences microRNA other sequences. has significantly expanded Cas12a-based diagnostic toolbox opened new avenues for detection.

Language: Английский

Citations

2
Identification of clinically relevant biomarkers of epileptogenesis — a strategic roadmap DOI
Michele Simonato, Denes V. Agoston, Amy R. Brooks‐Kayal

et al.

Nature Reviews Neurology, Journal Year: 2021, Volume and Issue: 17(4), P. 231 - 242

Published: Feb. 16, 2021

Language: Английский

Citations

79
Non-coding RNA in the wiring and remodeling of neural circuits DOI Creative Commons
Michael Soutschek, Gerhard Schratt

Neuron, Journal Year: 2023, Volume and Issue: 111(14), P. 2140 - 2154

Published: May 24, 2023

Language: Английский

Citations

37
Determinants of Functional MicroRNA Targeting DOI Open Access
Hyeonseo Hwang, Hee Ryung Chang,

Daehyun Baek

et al.

Molecules and Cells, Journal Year: 2023, Volume and Issue: 46(1), P. 21 - 32

Published: Jan. 1, 2023

MicroRNAs (miRNAs) play cardinal roles in regulating biological pathways and processes, resulting significant physiological effects.To understand the complex regulatory network of miRNAs, previous studies have utilized massivescale datasets miRNA targeting attempted to computationally predict functional targets miRNAs.Many target prediction tools been developed are widely used by scientists from various fields biology medicine.Most these consider seed pairing between miRNAs their mRNA additionally other determinants improve accuracy.However, exhibit limited accuracy high false positive rates.The utilization additional determinants, such as RNA modifications RNA-binding protein binding sites, may further prediction.In this review, we discuss that currently potentially predictive but unappreciated accuracy.

Language: Английский

Citations

29
Astrocytes as a target for therapeutic strategies in epilepsy: current insights DOI Creative Commons
Nihan Çarçak, Filiz Onat, Evgenia Sitnikova

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: July 31, 2023

Astrocytes are specialized non-neuronal glial cells of the central nervous system, contributing to neuronal excitability and synaptic transmission (gliotransmission). play a key roles in epileptogenesis seizure generation. Epilepsy, as chronic disorder characterized by hyperexcitation hypersynchronization, is accompanied substantial disturbances impairment astrocytic functions signaling. Anti-seizure drugs that provide symptomatic control seizures primarily target neural activity. In epileptic patients with inadequate available anti-seizure drugs, novel therapeutic candidates needed. These should treat epilepsy anti-epileptogenic disease-modifying effects. Evidence from human animal studies shows astrocytes have value for developing new drugs. this review, we present hyperexcitability activity following an etiology-based approach. We analyze role both development (epileptogenesis) generation (ictogenesis). Several promising strategies attempted modify astroglial treating being developed: (1) selective targeting glia-related molecular mechanisms glutamate transport; (2) modulation tonic GABA release astrocytes; (3) gliotransmission; (4) Kir4.1-BDNF system; (5) Na+/K+/ATPase activity; (6) DNA hypo- or hypermethylation candidate genes (7) gap junction regulators; (8) adenosine kinase (the major adenosine-metabolizing enzyme); (9) microglia-astrocyte communication inflammatory pathways. Novel now been developed, such astroglia-targeted gene therapy broad spectrum genetic constructs cells.

Language: Английский

Citations

29
Urinary biomarkers in diabetic nephropathy DOI
Elahe Soltani Fard, Sina Taghvimi, Farzaneh Karimi

et al.

Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 561, P. 119762 - 119762

Published: June 5, 2024

Language: Английский

Citations

11
From Serendipity to Precision: Integrating AI, Multi-Omics, and Human-Specific Models for Personalized Neuropsychiatric Care DOI Creative Commons
Masaru Tanaka

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 167 - 167

Published: Jan. 12, 2025

Background/Objectives: The dual forces of structured inquiry and serendipitous discovery have long shaped neuropsychiatric research, with groundbreaking treatments such as lithium ketamine resulting from unexpected discoveries. However, relying on chance is becoming increasingly insufficient to address the rising prevalence mental health disorders like depression schizophrenia, which necessitate precise, innovative approaches. Emerging technologies artificial intelligence, induced pluripotent stem cells, multi-omics potential transform this field by allowing for predictive, patient-specific interventions. Despite these advancements, traditional methodologies animal models single-variable analyses continue be used, frequently failing capture complexities human conditions. Summary: This review critically evaluates transition serendipity precision-based in research. It focuses key innovations dynamic systems modeling network-based approaches that use genetic, molecular, environmental data identify new therapeutic targets. Furthermore, it emphasizes importance interdisciplinary collaboration human-specific overcoming limitations Conclusions: We highlight precision psychiatry’s transformative revolutionizing care. paradigm shift, combines cutting-edge systematic frameworks, promises increased diagnostic accuracy, reproducibility, efficiency, paving way tailored better patient outcomes

Language: Английский

Citations

1
Serum-tolerant polymeric complex for stem-cell transfection and neural differentiation DOI Creative Commons
Yi Jin, Guochen Han,

Yuemei Gao

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 27, 2025

Mesenchymal stem cell (MSC) therapy holds promise in biomedical applications but faces challenges efficient transfection without compromising viability. Here, we show a serum-tolerant MSC nanotool, APOs@BP, composed of an apolipoprotein (APO) corona and boronated polyethyleneimine (BP) core. The APOs corona's serum-protein resistance cytomembrane affinity enable APOs@BP to achieve 10.4-fold higher efficiency improved cytocompatibility serum-containing medium compared high-molecular-weight polycationic transfectants. For neural differentiation, miRNA-124 all-trans retinoic acid derivative (atRAN) are further loaded into forming polymeric complex for sequential drug release triggered by lysosomal cytosolic reactive oxygen species post-transplantation. Transcriptomic analysis confirms that this system enhances differentiation through activation atRAN-induced potential miRNA-124-directed neurogenesis via cGMP-PKG, MAPK, PI3K-Akt pathways. Transplantation engineered MSCs reconstructs circuits alleviates cognitive impairment Alzheimer's disease model mice. Collectively, provides robust convenient method MSC-based regenerative medicine. Stem therapies have huge face challenges. the authors report on assembly with corona, carry stem-cell differentiation.

Language: Английский

Citations

1